The present invention is in the general field of animal therapy and relates to the treatment and prevention of bone disorders such as osteoporosis, osteoarthritis and the like, especially in humans.
The invention especially relates to the use of metal alumino silicates such as zeolites, particularly zeolite A, in the treatment of the aforesaid bone disorders.
It is therefore an important object of the present invention to provide a therapy for the treatment of the aforesaid bone disorders utilizing zeolites.
In the poultry industry, one of the problems prevalent throughout the industry is the legs of male breeders. The productive life of a female broiler breeder, for example, is nine months while the male broiler breeders have to be replaced after six months or sometimes even earlier. This early replacement is necessitated because of a breakdown in the legs of the males, thus limiting the frequency of mating. Male mortality rate is also about three to four times that of the female rate and this high rate is largely associated with leg problems. One of the major causes of the leg problems in poultry is a disease called tibial dyschondroplasia. Other less frequent causes are femur head necrosis and twisted leg disease.
It is therefore an important object of the present invention to inhibit the formation in poultry of the disease, tibial dyschondroplasia or other bone related diseases.
Applicants' parent application discloses the effectiveness of including a small amount of zeolite A in the feed formulation of laying hens in increasing the quality or stength of the egg shells of the eggs produced by the hens without decreasing egg production or having any deleterious effect on the eggs themselves. Application Ser. No. 475,370 is hereby incorporated herein in its entirety.
Over the years a wide variety of experiments have been conducted throughout the world utilizing zeolites of many different types in the feeding of animals for varying reasons. Most of these experiments have been in animal nutrition or in increasing the production of food animals or their food products. Most of the animals fed zeolites were poultry, cattle, sheep and swine. Zeolites fed to the animals were mainly naturally occurring zeolites or those zeolites found in nature. Although some degree of success in some areas was achieved, most of the results were unfavorable.
An article by C. Y. Chung et al from Nongsa Sihom Youngu Pogo 1978, 20 (Livestock) pp. 77-83 discusses the effects of cation exchange capacity and particle size of zeolites on the growth, feed efficiency and feed materials utilizability of broilers or broiling size chickens. Supplementing the feed of the broilers with naturally occurring zeolites, such as clinoptilolite, some increase in body weight gain was determined. Chung et al also reported that earlier results at the Livestock Experiment Station (1974, 1975, 1976--Suweon, Korea) showed that no significant difference was observed when 1.5, 3, and 4.5 percent zeolite was added to chicken layer diets.
U.S. Pat. No. 3,836,676 issued to Chukei Komakine in 1974 discloses the use of zeolites as an adsorbent for adhesion moisture of ferrous sulfate crystals in an odorless chicken feed comprising such crystals and chicken droppings. The results were said to be no less than those in the case where chickens were raised with ordinary feed.
Experiments have been in progress in Japan since 1965 on the use of natural zeolite minerals as dietary supplements for poultry, swine and cattle. Significant increases in body weight per unit of feed consumed and in the general health of the animals was reported (Minato, Hideo, Koatsugasu 5:536, 1968). Reductions in malodor were also noted.
Using clinoptilolite and mordenite from northern Japan, Onagi, T. (Rept. Yamagata Stock Raising Inst. 7, 1966) found that Leghorn chickens required less food and water and gained as much weight in a two-week trial as birds receiving a control diet. No adverse effects on health or mortality were noted. The foregoing Japanese experiments were reported by F. A. Mumpton and P. H. Fishman in the Journal of Animal Science, Vol. 45, No. 5 (1977), pp. 1188-1203.
Canadian patent No. 939,186 issued to White et al in 1974 (U.S. Pat. No. 4,393,082 issued July 12, 1983) discloses the use of zeolites having exchangeable cations as a feed component in the feeding of urea or biuret non-protein nitrogen (NPN) compounds to ruminants, such as cattle, sheep and goats. Natural and synthetic as well as crystalline and non-crystalline zeolites are disclosed. Zeolites tested using in vitro techniques included natural zeolites, chabazite and clinoptilolite and synthetic zeolites X, Y, F, J, M, Z, and A. Zeolite F was by far the most outstanding and zeolite A was substantially ineffective.
An article by W. L. Willis et al entitled "Evaluation of Zeolites Fed to Male Broiler Chickens" published in Poultry Science, Volume 61, Number 3, p. 438-442 (March, 1982) discloses the feeding of natural zeolites such as clinoptilolite to male broiler chickens in amounts of 1, 2 and 3 weight percent.
In a study at the University of Georgia, both broilers and layers were fed small amounts (about 2%) of clinoptilolite, a naturally occurring zeolite from Tilden, Tex. The egg shells from the hens receiving zeolite were slightly more flexible as measured by deformation, slightly less strong as measured by Instron breaking strength, and had a slightly lower specific gravity. The differences in egg shell quality were very small. This type of zeolite was ineffective in producing a stronger egg shell. An article written by Larry Vest and John Shutze entitled "The Influence of Feeding Zeolites to Poultry Under Field Conditions" summarizing the studies was presented at Zeo-Agriculture '82.
A study of H. S. Nakaue of feeding White Leghorn layers clinoptilolite, reported in 1981 Poultry Science 60:944-949, disclosed no significant differences in egg shell strength between hens receiving the zeolite and hens not receiving the zeolite.
European Patent Application No. 011992 published Sept. 26, 1984 discloses the feeding of the natural zeolite, chabazite, to poultry, namely turkeys. In a test utilizing 480 tom turkeys, those turkeys fed 2 weight percent chabazite ore showed improved weight gain and feed efficiency over those turkeys fed similar amounts of sodium exchanged zeolite A and calcium exchanged zeolite A; however, the turkeys fed zeolites showed an increase in mortality rate over those turkeys in which no zeolites were fed. The turkeys fed sodium exchanged zeolite A showed significantly less weight gain and less feed efficiency than those turkeys fed no zeolites at all and the turkeys fed calcium exchanged zeolite A showed about the same weight gain as the control, but had even less feed efficiency than the turkeys fed the sodium exchanged zeolite A.
Japanese patent No. 59-203450 published Nov. 17, 1984 describes the use of synthetic metal aluminosilicates, preferably type A, type P, type X or type Y zeolites, as feed additives for livestock, pets, cultured fish, etc. with active ingredients consisting of basicity-adjusted aluminosilicates to an equilibrium pH of 10.5 or less. The feed additives are said to have a digestion-regulating effect, i.e., a high antacid effect in the pH range of 3 to 5. They also are said to appear to be superior as Co++ donors and donors of other minerals. In a single experiment of 100 piglets, using 2 weight percent calcium aluminosilicate, either amorphous or type A zeolite, no significant differences between the two forms were observed. Body weight for piglets fed the calcium zeolites showed an increase but feed utilization weight was down slightly.
Zeolites are crystalline hydrated aluminosilicates of alkali and alkaline earth cations, having infinite, three-dimensional structures.
Zeolites consist basically of a three-dimensional framework of SiO.sub.4 and AlO.sub.4 tetrahedra. The tetrahedra are crosslinked by the sharing of oxygen atoms so that the ratio of oxygen atoms to the total of the aluminum and silicon atoms is equal to two or O/(Al+Si)=2. The electrovalence of each tetrahedra containing aluminum is balanced by the inclusion in the crystal of a cation, for example, a sodium ion. This balance may be expressed by the formula Al/Na=1. The spaces between the tetrahedra are occupied by water molecules prior to dehydration.
There are a number of different types of zeolites. Some zeolites are found in nature and are made synthetically. Other zeolites are made only synthetically. Zeolite A is not found in nature and is made only synthetically.
Zeolite A may be distinguished from other zeolites and silicates on the basis of their composition and X-ray powder diffraction patterns and certain physical characteristics. The X-ray patterns for these zeolites are described below. The composition and density are among the characteristics which have been found to be important in identifying these zeolites.
The basic formula for all crystalline sodium zeolites may be represented as follows: EQU Na.sub.2 O.Al.sub.2 O.sub.3.xSiO.sub.2.yH.sub.2 O.
In general, a particular crystalline zeolite will have values for "x" and "y" that fall in a definite range. The value "x" for a particular zeolite will vary somewhat since the aluminum atoms and the silicon atoms occupy essentially equivalent positions in the lattice. Minor variations in the relative number of these atoms do not significantly alter the crystal structure or physical properties of the zeolite. For zeolite A, the "x" value normally falls within the range 1.85.+-.0.5.
The value for "y" is not necessarily an invariant for all samples of zeolites. This is true because varous exchangeable ions are of different size, and, since there is no major change in the crystal lattice dimensions upon ion exchange, the space available in the pores of the zeolite to accommodate water molecules varies.
The average value for "y" for zeolite A is 5.1. The formula for zeolite A may be written as follows: EQU 1.0.+-.0.2Na.sub.2 O.Al.sub.2 O.sub.3.1.85.+-.0.5SiO.sub.2.yH.sub.2 O.
In the formula, "y" may be any value up to 6.
An ideal zeolite A has the following formula: EQU (NaAlSiO.sub.4).sub.12.27H.sub.2 O
Among the ways of identifying zeolites and distinguishing them from other zeolites and other crystalline substances, the X-ray powder diffraction pattern has been found to be a useful tool. In obtaining the X-ray powder diffraction patterns, standard techniques are employed. The radiation is the K.alpha. doublet of copper and a Geiger counter spectrometer with a strip chart pen recorder is used. The peak heights, I, and the positions as a function of 2.theta. where .theta. is the Bragg angle, are read from a spectrometer chart. From these, the relative intensities, 100 I/I.sub.O, where I.sub.o is the intensity of the strongest line or peak and d the interplanar spacing in angstroms corresponding to the recorded lines are calculated.
X-ray powder diffraction data for a sodium zeolite A are given in Table I.
TABLE I ______________________________________ X-RAY DIFFRACTION PATTERN FOR ZEOLITE A h.sup.2 + k.sup.2 + 1.sup.2 d (.ANG.) ##STR1## ______________________________________ 1 12.29 100 2 8.71 70 3 7.11 35 4 6.15 2 5 5.51 25 6 5.03 2 8 4.36 6 9 4.107 35 10 3.895 2 11 3.714 50 13 3.417 16 14 3.293 45 16 3.078 2 17 2.987 55 18 2.904 10 20 2.754 12 21 2.688 4 22 2.626 20 24 2.515 6 25 2.464 4 26 2.414 &gt;1 27 2.371 3 29 2.289 1 30 2.249 3 32 2.177 7 33 2.144 10 34 2.113 3 35 2.083 4 36 2.053 9 41 1.924 7 42 1.901 4 44 2.858 2 45 1.837 3 49 1.759 2 50 1.743 13 53 1.692 6 54 1.676 2 55 1.661 2 57 1.632 4 59 1.604 6 ______________________________________
The more significant d values for zeolite A are given in Table II:
TABLE II ______________________________________ MOST SIGNIFICANT d VALUES FOR ZEOLITE A d Value of Reflection in .ANG. ______________________________________ 12.1 .+-. 0.2 8.7 .+-. 0.2 7.10 .+-. 0.15 5.50 .+-. 0.10 4.10 .+-. 0.10 3.70 .+-. 0.07 3.40 .+-. 0.06 3.29 .+-. 0.05 2.98 .+-. 0.05 2.62 .+-. 0.05 ______________________________________
Occasionally, additional lines not belonging to the pattern for the zeolite appear in a pattern along with the X-ray lines characteristic of that zeolite. This is an indication that one or more additional crystalline materials are mixed with the zeolite in the sample being tested. Small changes in line positions may also occur under these conditions. Such changes in no way hinder the identification of the X-ray patterns as belonging to the zeolite.
The particular X-ray technique and/or apparatus employed, the humidity, the temperature, the orientation of the powder crystals and other variables, all of which are well known and understood to those skilled in the art of X-ray crystallography or diffraction can cause some variations in the intensities and positions of the lines. These changes, even in those few instances where they become large, pose no problem to the skilled X-ray crystallographer in establishing identities. Thus, the X-ray data given herein to identify the lattice for a zeolite, are not to exclude those materials which, due to some variable mentioned or otherwise known to those skilled in the art, fail to show all of the lines, or show a few extra ones that are permissible in the cubic system of that zeolite, or show a slight shift in position of the lines, so as to give a slightly larger or smaller lattice parameter.
A simpler test described in "American Mineralogist", Vol. 28, page 545, 1943, permits a quick check of the silicon to aluminum ratio of the zeolite. According to the description of the test, zeolite minerals with a three-dimensional network that contains aluminum and silicon atoms in an atomic ratio of Al/Si=2/3=0.67, or greater, produce a gel when treated with hydrochloric acid. Zeolites having smaller aluminum to silicon ratios disintegrate in the presence of hydrochloric acid and precipitate silica. These tests were developed with natural zeolites and may vary slightly when applied to synthetic types.
U.S. Pat. No. 2,882,243 describes a process for making zeolite A comprising preparing a sodium-aluminum-silicate water mixture having an SiO.sub.2 :Al.sub.2 O.sub.3 mole ratio of from 0.5:1 to 1.5:1, and Na.sub.2 O mole ratio of from 35:1 to 200:1, maintaining the mixture at a temperature of from 20.degree. C. to 175.degree. C. until zeolite A is formed, and separating the zeolite A from the mother liquor.
It is an important object of this invention to provide a method of improving the bone strength or bone quality of animals, including humans, by treatment of the animals with a relatively small amount of metal alumino silicates, especially zeolites.
It is an object of the invention to provide an animal treatment or feed containing zeolite, which inhibits bone disorders in animals, especially humans, such as osteoporosis, osteoarthritis, tibial dyschondroplasia, femur head necrosis and the like.
Another object of the invention is to provide a process for the treatment and/or prevention of bone disorders in animals wherein an effective amount of zeolite is added to the diet of the animal.
It is also an important object of the present invention to provide an improved feed formulation for poultry which contains a small amount of zeolite.
Still another object of the invention is to effectively increase bone strength in animals without causing any deleterious effects in the animals.
Yet a further object of the present invention is to increase the strength of bones in poultry.
Other objects and advantages of the invention will be more fully understood from a reading of the description and claims hereinafter.